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Construction and application of covalently bonded CD147 cell membrane chromatography model based on polystyrene microspheres

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Abstract

In this study, a novel cell membrane chromatography (CMC) model was developed to investigate cluster of differentiation 147 (CD147) targeted anti-tumor drug leads for specific screening and ligand-receptor interaction analysis by SNAP-tagged CD147 fusion protein conjugation and polystyrene microspheres (PS) modification. Traditional Chinese medicines (TCMs) are widely used in the treatment of cancer. CD147 plays important roles in tumor progression and acts as an attractive target for therapeutic intervention; therapeutic drugs for CD147-related cancers are limited to date. Thus, a screening method for active components in TCMs is crucial for the further research and development of CD147 antagonists. However, improvement is still needed to perform specific and accurate drug lead screening using the CMC-based method. Recently, our group developed a covalently immobilized receptor-SNAP-tag/CMC model using silica gel as carrier. Besides the carboxyl group on multi-step modified silica particles, the amino group of benzyl-guanine (BG, substrate of SNAP-tag) also possesses reactivity towards the carboxyl group on available carboxyl-modified PS. Herein, we used PS as carrier and an extended SNAP-tag with CD147 receptor to construct the PS-BG-CD147/CMC model for active compound investigation coupled with HPLC/MS and applied this coupled PS-BG-CD147/CMC-HPLC/MS two-dimensional system to drug lead screening from Nelumbinis Plumula extract (NPE) sample. In addition, to comprehensively verify the pharmacological effects of screened ingredients, a cell proliferation inhibition assay was performed, and the interaction between the ingredients and CD147 was studied by the frontal analysis method. This study developed a high-throughput PS-based CMC screening platform, which could be widely applied and utilized in chromatographic separation and drug lead discovery.

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Abbreviations

CMC:

Cell membrane chromatography

CD147:

Cluster of differentiation 147

PS:

Polystyrene microspheres

TCMs:

Traditional Chinese medicines

BG:

Benzyl-guanine

NPE:

Nelumbinis Plumula extract

CMSP:

Cell membrane stationary phase

PS-COOH:

Carboxylate polystyrene microspheres

PS-BG-CMSP:

Polystyrene-based cell membrane stationary phase

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Funding

This work was supported by the National Natural Science Foundation of China (82104118, 81973278, and 81930096).

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Author notes

  1. Yanni Lv and Saisai Wang contributed equally to this work.

Authors and Affiliations

  1. School of Pharmacy, Xi’an Jiaotong University, 76# Yanta Westroad, Xi’an, Shaanxi, 710061, People’s Republic of China

    Yanni Lv, Saisai Wang, Yamin Wang, Xin Zhang, Qianqian Jia, Shengli Han & Langchong He

  2. Institute of Pharmaceutical Science and Technology, Western China Science &Technology Innovation Harbour, Xi’an, Shaanxi, 710115, People’s Republic of China

    Yanni Lv, Saisai Wang, Yamin Wang, Xin Zhang, Qianqian Jia, Shengli Han & Langchong He

  3. Jiangsu Chia Tai-Tianqing Pharmaceutical Co., Ltd. Lianyungang, Jiangsu, 222062, People’s Republic of China

    Saisai Wang

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  1. Yanni Lv
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Lv, Y., Wang, S., Wang, Y. et al. Construction and application of covalently bonded CD147 cell membrane chromatography model based on polystyrene microspheres. Anal Bioanal Chem 415, 1371–1383 (2023). https://doi.org/10.1007/s00216-023-04528-7

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